Table 2. Summary of clinical and necropsy findings.
Fetal ID | ZF1 | ZF2 | ZF3 | ZF4 | ZF5 | CF3 | CF4 |
Dam ID | ZD1 | ZD2 | ZD3 | ZD4 | ZD5 | CD3 | CD4 |
Inoculum | ZIKV | ZIKV | ZIKV | ZIKV | ZIKV | Saline | None |
GD of Inoculation | 54 | 55 | 53 | 55 | 53 | 55 | N/A |
GD of Delivery | 118 | 126 | 145 | 149 | 148 | 146 | 145 |
GD (PD) of Demise | 118 (0) | 128 (2) | 162 (17) | 166 (17) | 165 (17) | 167 (21) | 354 (209) |
Pregnancy and Neonatal Outcome | Early cervical ripening, pPROM, emergency hysterotomy with fetal euthanasia | Early cervical ripening, clinically indicated hysterotomy, neonatal death (septicemia) | Elective hysterotomy, live birth, clinically indicated euthanasia | Elective hysterotomy, live birth, experimental euthanasia | Elective hysterotomy, live birth, experimental euthanasia | Elective hyster-otomy, live birth, experimental euthanasia | Elective hyster-otomy, live birth, experimental euthanasia |
Maternal Utero-placental Pathology | Small mono-discoidal placenta; multifocal infarctions, hemorrhage, villous stromal mineralization and perivasculitis | Endometritis and myometritis; plasmacytic deciduitis; villous stromal mineralization | Multifocal infarctions, acute and chronic hemorrhage, villous fibrin deposition and stromal mineralization | Multifocal infarctions, villous fibrin deposition and mineralization, neutrophilic and plasmacytic deciduitis, decidual leukocytoclastic vasculitis | Focal infarction, villous fibrin deposition and mineralization, neutrophilic and plasmacytic deciduitis, mild decidual leuko-cytoclastic vasculitis | NP | Rare stromal mineralization, focal infarction |
Neonatal Clinical Presentation | N/A | Prolonged hypoxemia during resuscitation, hyperglycemia, hypotonia, bradycardia, apnea, cardio-respiratory arrest | Seizures, tachypnea, cardiomegaly, axial hypotonia, lower limb weakness, dysphagia, retarded growth | Possible mild auditory impairment complicated by presence of earwax | NSF | NSF | NSF |
Fetal Gross Pathology | NSF | Cerebral meningeal and ventricular hemorrhage secondary to sepsis; small cerebellum; chin dermatitis | Cardiomegaly with mild dilation of right and left ventricles; reduced brain mass | NSF | NSF | NSF | NSF |
Fetal CNS Lesions |
Cerebrum—Multifocal periventricular mineralization; ependymal degeneration; increased apoptosis of neuroprogenitor cell population; increased cells noted in molecular layer of one section, presumed immature neurons (GFAP-/Iba1-/CD45-); increased astrocytes (GFAP+) in molecular layer of cingulate gyrus Cerebellum–Moderate decrease in Purkinje cell population Spinal cord—Mild to marked rarefaction and edema of white matter, thoracic cord is more affected |
Multifocal hemorrhage, edema and necrosis secondary to sepsis. Pathologies atypical to sepsis cannot be conclusively attributed to Zika virus infection: Cerebrum—Periventricular mineralization, increased apoptosis of neuroprogenitor cells Cerebellum–Minimal decrease in Purkinje cell population, decreased density of external granular layer |
Cerebrum—Ventricular dilation, mild ependymal loss; fewer neuroprogenitor cells Cerebellum—Attenuation of the external granular cell layer; moderate decrease in Purkinje cell population Spinal cord—Glial necrosis, white matter, minimal in lumbar cord |
Cerebrum—Unilateral periventricular ependymal cell degeneration and loss, focally extensive Cerebellum—Multifocal, minimal decrease in Purkinje cell population |
Cerebellum—Multifocal, moderate decrease in Purkinje cell population and decrease in external granular cell layer Spinal cord—Swollen myelin sheaths, rare gitter cells and solitary spheroid in cervical cord Dorsal root ganglion—Scattered, minimal lymphocytic infiltrates |
NSF | No gross lesions; microscopic lesions not assessed |
Fetal Lesions in Other Tissues | Urinary bladder—Multifocal, minimal histiocytic infiltrates |
Skin of chin—Focal, mild, neutrophilic dermatitis Biceps brachii, left—Hemorrhage and edema secondary to sepsis Brachioradialis, right—Hemorrhage and edema secondary to sepsis |
Heart—Cardiomyopathy, left ventricle, increased cardiomyofiber diameter, cardiomyocyte karyomegaly | Heart—Ventricle, cardiomyocyte hypertrophy and karyomegaly, rare | Heart—Multifocal, mild to moderate cardiomyocyte vacuolar degeneration and multifocal, mild karyomegaly | NSF | NSF |
Fetal Post-mortem MRI | NP | T1W and T2W lesions secondary to sepsis | Reduced brain volume and surface area | NSF | NSF | NSF | NP |
NSF = no significant findings, NP = not performed/not assessed, N/A = not applicable.